Rat mitochondrial ATP synthase ATP5G3: cloning and upregulation in pancreas after chronic ethanol feeding

Abstract

Individuals with chronic excessive alcohol ingestion are put at the risk of acute and chronic pancreatitis. Underlying molecular mechanisms are unknown. Differential gene expression in the pancreas was profiled using mRNA differential display by comparison between control and ethanol-consuming rats. Male Wistar rats were fed with diets containing 6.7% (vol/vol) ethanol for 4 wk. A cDNA tag that was overexpressed in the pancreas of rats fed ethanol was isolated. A 723-bp cDNA was cloned from a rat pancreatic cDNA library, which encodes a novel rat mitochondrial ATP synthase subunit 9, isoform 3 (ATP5G3), which is homologous to a human ATP5G3 gene. Real-time PCR demonstrated that all three nuclear gene isoforms (ATP5G1, ATP5G2, and ATP5G3) were consistently upregulated in the pancreas of alcohol-consuming rats, parallel with mitochondrial injury. The cellular response to mitochondrial damage and metabolic stress may reflect an adaptive process for mitochondrial repair in pancreatic acinar cells during chronic ethanol ingestion.

Anticancer effects of amooranin in human colon carcinoma cell line in vitro and in nude mice xenografts

“…One of the up-regulated gene, ATP synthase H1 transporting, isoform 3 (ATP5G3), plays a role in the generation of a mitochondrial membrane potential by hydrolysis of ATP and may correlate with the altered potential of AMRtreated cells in vitro. 43,44 Another major apoptotic gene, caspase 3, was up regulated 2.3-fold, 5.1-fold and 6.3-fold by 2, 5 and 10 mg/ kg AMR treatment in xenograft tumors. Apart from these direct effects, several transcription factors (PTMA, HCFC1, NFE2L3, DHX9, TAF12, HOXD3) and transcription regulatory proteins (MID1, PTTG1, RB1, CDK2AP1, MTA2, SP100) were also upregulated by AMR.…”

Calcium signalling and pancreatic cell death: apoptosis or necrosis?

“…Such mitochondrial inhibition appears to provoke compensatory protective measures in the cell, including an upregulation of mitochondrial ATP synthase, observed after both cerulein hyperstimulation and chronic alcohol exposure. 85 The importance of ATP depletion for pancreatic acinar cell fate is further underscored by experiments in which addition of ATP to the cell interior, administered via a patch pipette, was able to reverse the detrimental Ca 2 þ signals induced by alcohol metabolites. For example, FA-induced sustained cytosolic Ca 2 þ rises, via the release from ER Ca 2 þ stores and subsequent Ca 2 þ entry, were completely abolished in cells receiving supplementary ATP, whereas control cells produced large, sustained elevations of cytosolic Ca 2 þ (Figure 4) 12 that cause cellular necrosis.…”

Animal Models in Alcoholic Pancreatitis — What Can We Learn?

“…Ethanol-induced mitochondrial dysfunction was suggested to account for pancreatic steatosis, but again results were conflicting. After long-term ethanol administration, some authors observed pancreatic mitochondrial damage such as swelling and formation of giant mitochondria, fragmentation of the internal membranes and damaged cristae in the rat [32,[46][47][48][49], others did not report these alterations [36,45]. In another study with Lieber-DeCarli ethanol-fed rats, Wilson et al [50] isolated functional mitochondria from the rat pancreas and measured respiratory parameters.…”